The present invention relates to controlled release unit dose formulations of pharmaceuticals. In the prior art many techniques have been used to provide controlled and extended release pharmaceutical dosage forms in order to maintain therapeutic serum levels of medicaments and to minimize the effects of missed doses of drugs caused by a lack of patient compliance.
In the prior art extended release tablets containing osmotic tablets containing water insoluble drugs have been described which have had an osmotically active drug core surrounded by a semipermeable membrane. The core is divided into two layers one of which contains the active drug and the other contains a push layer of pharmacologically inactive ingredients which are osmotically active in the presence of gastrointestinal fluids. An outer water impermeable coating covers the tablet which is provided with an aperture that is formed by laser drilled orifice to allow gastrointestinal fluids to reach the osmotic push layer to activate the tablet and to begin to push out the active medicament. A product of this type is disclosed in U.S. Pat. No. 4,783,337 and is sold commercially as Procardia XL.RTM..
The osmotic dosage forms that are disclosed in U.S. Pat. No. 4,783,337 are described as having a passageway which includes an aperture, orifice, hole, porous element, hollow fiber, capillary tube, microporous insert, pore, microporous overlay or bore which extends through the semipermeable lamina, the microporous lamina, or through the laminated wall. The patent also states that the passageway may be formed by mechanical drilling, laser drilling, eroding an erodible element, extracting, dissolving, bursting or leaching a passageway-former from the wall of the osmotic dosage form (col. 14, line 35 et seq.) which are implicitly pre-formed in the tablet during the manufacturing process. The only exemplified technique of forming a passageway in U.S. Pat. No. 4,783,337 is the use of a laser to drill a hole in the outer layer of the tablet.
U.S. Pat. No. 4,285,987 described an osmotic tablet which had a laser drilled aperture into the core of the tablet. The laser drilled hole was plugged with leachable sorbitol which was leached out in the presence of gastrointestinal fluid.
U.S. Pat. No. 3,845,770 discloses an osmotic dispensing device for soluble drugs or soluble derivatives of drugs. That device has an external membrane, a compartment with a soluble active agent and an osmotic agent and an osmotic passageway which allows external fluid to be continuously imbibed.
U.S. Pat. No. 4,801,461 discloses a dosage form which provides for the controlled release of pseudoephedrine over an extended period of time. The dosage form contains an osmagent such as sodium chloride and hydroxypropyl methyl cellulose and is provided with a passageway.
U.S. Pat. No. 4,016,880 describes an osmotic tablet which has one or more openings in the side wall which are formed in situ and allow gastrointestinal fluids to have access to the core of the tablet.
The present invention is concerned with providing an osmotic tablet that is designed to provide once a day dosing of water soluble drugs but does not have a pre-formed osmotic passageway. In addition the osmotic tablet of the invention is designed to avoid the need to have a separate "push" layer in the core which contains no medicament and which avoids the need to have a pre-formed passageway or a leachable plug in the tablet to allow the gastrointestinal fluid to reach the osmotic core.